4.6 Review

Cellular complexity in brain organoids: Current progress and unsolved issues

Journal

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 111, Issue -, Pages 32-39

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2020.05.013

Keywords

Brain organoids; Cerebral organoids; Self-organization; Pluripotent stem cells; Vascularization; Microglia; Transplantation

Funding

  1. American Heart Association [19PABH134610000]
  2. The Paul G. Allen Frontiers Group [19PABH134610000]
  3. Paul G Allen Family Foundation
  4. Leona M and Harry B Helmsley Charitable Trust Grant [2017-PG-MED001]
  5. G Harold and Leila Y Mathers Foundation
  6. JPB Foundation
  7. Ray and Dagmar Dolby Family Fund
  8. Grace Foundation
  9. EMBO Postdoctoral Long-term Fellowship (ALTF) [1214-2014]
  10. Human Frontiers Science Program (HFSP Long-Term Fellowship) [LT001074/2015]
  11. German Research Foundation (DFG)
  12. NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Leichtung Family Investigator)

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Brain organoids, derived from pluripotent stem cells through self-organization, are three-dimensional neural aggregates that mimic certain brain regions. They present an exciting area of research for studying human brain development, function, and dysfunction in new ways. Strategies including complementing neuroectodermal models with non-neuronal cell types, as well as transplantation approaches for higher cellular complexity and long-term survival, have been discussed in recent discoveries.
Brain organoids are three-dimensional neural aggregates derived from pluripotent stem cells through self-organization and recapitulate architectural and cellular aspects of certain brain regions. Brain organoids are currently a highly exciting area of research that includes the study of human brain development, function, and dysfunction in unprecedented ways. In this Review, we discuss recent discoveries related to the generation of brain organoids that resemble diverse brain regions. We provide an overview of the strategies to complement these primarily neuroectodermal models with cell types of non-neuronal origin, such as vasculature and immune cells. Recent transplantation approaches aiming to achieve higher cellular complexity and long-term survival of these models will then be discussed. We conclude by highlighting unresolved key questions and future directions in this exciting area of human brain organogenesis.

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